Effect of propofol on vascular reactivity in thoracic aortas from rats with endotoxemia

BackgroundThis study examined the effect of propofol on thoracic aortas isolated from endotoxic rats to assess endothelium-dependent and -independent relaxant responses.MethodsAdult male Wistar rats were assigned randomly to one of two groups, a saline control group or an experimental group treated with lipopolysaccharide (LPS, 10 mg/kg intravenously). At 6 hours after saline or LPS infusion, the thoracic aorta was excised and cut into 3-mm rings. Aortic rings with or without endothelium were suspended in organ baths for isometric tension recording.ResultsBoth norepinephrine (NE)-induced vascular contraction and acetylcholine-induced vasodilation were attenuated in aortasfrom LPS-treated rats. Furthermore, preincubation with propofol caused a rightward shift in the NE concentration–response curve for aortasfrom LPS-treated rats compared to sham controls. The slow and sustained, but not the initial fast, contractile response to NE was significantly suppressed by propofol in LPS-treated aortas. In addition, vascular relaxation induced by propofol in LPS-treated aortas was partially suppressed by inhibitors of either nitric oxide (NO) synthase or soluble guanylate cyclase, but not bypotassium channel inhibitors.ConclusionThese data suggest that propofol reduces the sensitivity to NE in aortic rings from endotoxic rats. This appears to be caused by (i) blockade of the extracellular calcium influx rather than a reduction in intracellular calcium release and (ii) an increased response to, at least in part, NO–cGMP in rat aortas.